Graphical abstract

Cri-du-Chat syndrome (MIM 123450) is a chromosomal syndrome characterized by the characteristic features, including cat-like cry and chromosome 5p deletions. We report a family with five individuals showing chromosomal rearrangements involving 5p, resulting from rare maternal complex chromosomal rearrangements (CCRs), diagnosed post- and pre-natally by comprehensive molecular and cytogenetic analyses. Two probands, including a 4½-year-old brother and his 2½-year- old sister, showed no diagnostic cat cry during infancy, but presented with developmental delay, dysmorphic and autistic features. Both patients had an interstitial deletion del(5)(p13.3p15.33) spanning ∼26.22 Mb. The phenotypically normal mother had de novo CCRs involving 11 breakpoints and three chromosomes: ins(11;5) (q23;p14.1p15.31),ins(21;5)(q21;p13.3p14.1),ins(21;5)(q21;p15.31p15.33),inv(7)(p22q32)dn. In addition to these two children, she had three first-trimester miscarriages, two terminations due to the identification of the 5p deletion and one delivery of a phenotypically normal daughter. The unaffected daughter had the maternal ins(11;5) identified prenatally and an identical maternal allele haplotype of 5p. Array CGH did not detect any copy number changes in the mother, and revealed three interstitial deletions within 5p15.33-p13.3, in the unaffected daughter, likely products of the maternal insertions ins(21;5). Chromothripsis has been recently reported as a mechanism drives germline CCRs in pediatric patients with congenital defects. We postulate that the unique CCRs in the phenotypically normal mother could resulted from chromosome 5p chromothripsis, that further resulted in the interstitial 5p deletions in the unaffected daughter. Further high resolution sequencing based analysis is needed to determine whether chromothripsis is also present as a germline structural variation in phenotypically normal individuals in this family.

Objectives: Both low vitamin D status and metabolic syndrome (MetS) are worldwide concerns, and low 25hydroxyvitamin D [25(OH)D] levels are associated with MetS; however, related epidemiological evidence based on elderly Chinese individuals, especially those over 80 years of age, is limited. In the present study, we aimed to evaluate the association between serum 25(OH)D and MetS in elderly Chinese individuals. Method: Serum 25(OH)D was measured in a cross-sectional sample of 2493 elderly people aged 65-112 years from eight areas of China in which the density of centenarians is exceptionally high. MetS was diagnosed according to blood pressure, lipid, and blood sugar levels; waist circumference; and body mass index (BMI). Adjusted multivariable logistic regression was used to analyze the associations between vitamin D and MetS based on different diagnostic criterias. Results: A total of 890 (35.7%) of the recruited elderly individuals had insufficient levels of vitamin D, and 1029 participants (41.3%) were vitamin D deficient. High serum vitamin D concentrations were associated with a low prevalence of MetS according to the modified Adult Treatment Panel III (ATP III) criteria for adequate versus deficient vitamin D levels (OR: 0.63, 95% CI: 0.45, 0.88) and inadequate versus deficient vitamin D levels (OR: 0.70, 95% CI: 0.52, 0.92). Each 10 ng/ml increase in serum vitamin D was significantly associated with a decreased prevalence of MetS according to the modified ATP III criteria for people with normal waist circumference (WC) (OR: 0.55, 95% CI: 0.43,0.71). However, no significant statistical correlation was found among elderly people with a high WC. Additionally, in the analysis of the individual components, the ORs of adequate versus deficient vitamin D levels were 0.46 (95% CI: 0.30, 0.71) for elevated triglycerides and 0.64 (95% CI: 0.42, 0.97) for reduced high-density lipoprotein cholesterol (HDL-C) after adjustment for other components. Conclusions: Vitamin D deficiency is very common among elderly Chinese individuals. Vitamin D deficiency may be a risk factor for MetS; however, the association was only statistically significant among elderly people with noncentral obesity. Further studies are needed to examine the causal direction of the association.

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